Decision Resources, Inc., one of the world’s leading research and advisory firms for pharmaceutical and healthcare issues, came out with a press release today announcing that that Neurochem’s Alzhemed (tramiprosate) and Myriad Genetics’ Flurizan (R-flurbiprofen) will account for nearly 60% of the market to treat Alzheimer’s disease by 2015. Both drugs have shown promise in early clinical development, and will be the first treatments for Alzheimer’s disease that modify the course of the disease. Both agents will reach the U.S. market in 2008 and the European market by 2010.
Alzheimer’s disease is a progressive, neurodegenerative disease characterized by significant loss of function in more than one cognitive domain including memory, reasoning, and judgment. In the United States, France, Germany, Italy, Spain, the United Kingdom, and Japan, prevalent cases numbered more than 5.7 million in 2005.
The new Pharmacor report entitled Alzheimer’s Disease predicts that Alzhemed and Flurizan will account for 46% and 13% of sales, respectively, in the major pharmaceutical markets in 2015. The report also measures the extent to which upcoming patent expiries will reduce the market shares of the current mainstay classes of drugs used to treat Alzheimer’s disease-acetylcholinesterase inhibitors (AChEIs) and N-methyl-aspartate (NMDA) receptor antagonists. Drugs in these classes include Eisai/Pfizer’s donepezil, Novartis/Sigma-Tau/Esteve’s rivastigmine, Merz’s Axura, and Lundbeck’s Ebixa.
It is well-known that AChEIs and NMDAs merely stabilize or moderatly delay the cognitive decline that Alzheimer’s disease patients experience. What these type of agents cannot do is to modify the disease state. According to Kate Hohenberg, director at Decision Resources, Inc. “the need for more effective drugs for Alzheimer’s disease is so crucial that any agents that receive regulatory approval will capture market share. Alzhemed and Flurizan will likely show variable efficacy, but they will still capture a significant portion of the market to treat Alzheimer’s disease.”
It is still likely that the traditional acetylcholinesterase inhibitors (AChEIs) will continue to dominate the Alzheimer’s disease market for the next several years, with Eisai/Pfizer’s Aricept (donepezil) retaining a leadership position, and, to a lesser extent, Novartis’s Exelon (rivastigmine). However, sales of these drugs will decline because of the expiration of their patents. All agents in this class will lose patent protection by 2013.
And in what used to be a very radical theory regarding causation and linkage to Alzheimer’s, clinical trials now under way are testing the theory that the cause of Alzheimer’s disease is linked to diabetes. The trials are looking at whether the diabetes drug Avandia can slow or stop the progression of Alzheimer’s disease. Preliminary trials suggest that it can — at least in patients who do not carry the ApoE4 gene linked to earlier and faster-progressing Alzheimer’s disease.
According to Allen D. Roses, the theory behind the treatment predicts that the same processes that underlie diabetes also underlie Alzheimer’s disease and that a number of researchers find similarities between the metabolism of diabetes and the metabolism of Alzheimer’s disease.
Roses, now senior vice president for genetics research at GlaxoSmithKline, and Ann M. Saunders, PhD — his research partner and wife — describe the theory in detail in the April 2006 issue of Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association.
Roses isn’t the only Alzheimer’s researcher to back this controversial theory. But he’s among the most distinguished. In the early 1990s, Roses and colleagues were the first to link the ApoE4 gene to early-onset Alzheimer’s disease.
“We discovered that the ApoE gene is significantly associated with the common form of Alzheimer’s disease,” Roses says. “What wasn’t known is how it was operating in the brain. Over several years, we were doing experiments to see what the different forms of ApoE — ApoE4, ApoE3, and ApoE2 — were doing to metabolism in animals. We found a change in sugar utilization.”
The body has intricate, interconnected systems for controlling how its main fuel — sugar — is burned. In diabetes, the system is terribly out of whack, Roses states. [And,] it’s also out of whack in Alzheimer’s disease. He points to imaging studies showing that the brains of people who carry the ApoE4 gene have a lowered sugar-burning “thermostat.”
Roses reports that small clinical trials show that Avandia slightly improved mental function in patients with mild-to-moderate Alzheimer’s disease. But it only seems to work in patients who don’t carry the ApoE4 gene. Roses says the FDA has already approved a large-scale clinical trial of Avandia in genetically screened patients with Alzheimer’s disease. Until the results of this trial are known — and the results are years away — Roses strongly warns people not to try using Avandia as an Alzheimer’s treatment.
It will be interetsing to follow these new leads for Alzheimer’s drugs and whether or not there will actually be a drug presecribed for those who have a genetic predisposition to the disease in order to prevent or lessen its onset.
(SOURCES: Roses, A.D. and Saunders, A.M. Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association, April 2006; vol 2: pp 59-70. Risner, M.E. The Pharmacogenomics Journal, Jan. 31, 2006, advance online edition. Allen D. Roses, MD, senior vice president for genetics research, GlaxoSmithKline. Bill Theis, PhD, vice president for medical and scientific affairs, Alzheimer’s Association, Chicago.)
